During the past year, our studies concerning the adenosine receptor, the adenosine uptake site and the "peripheral type" and central type benzodiazepine receptors have continued to focus on the possible mechanisms whereby these neural systems modulate neuronal activity. We have succeeded in solubilizing both the adenosine receptor and uptake site and show that they remain distinct from one another. We have further characterized the interaction between calcium antagonists and the adenosine system and have completed a series of studies showing that chronic carbamazepine administration leads to an upregulation of adenosine receptors in the brain. The adenosine uptake site has been kinetically characterized in brain from five different species, showing that dipyridamole is a very poor inhibitor of nitrobenzylthioinosine binding in rat brain compared to guinea pig and human brain. Studies done in Maudsley reactive rats have shown no changes in brain benzodiazepine binding sites but have, for the first time, shown region specific alterations in adenosine receptors. We have also completed studies during the past year that have shown that the "peripheral type" benzodiazepine binding site is upregulated following chronic ethanol administration to rats and that this increase in the number of binding sites persists during ethanol withdrawal. Increases in brain (3H)Ro5-4864 binding sites are, therefore, associated with both dependence and withdrawal. The autoradiographic localization of adenosine uptake sites has been compared directly to that of adenosine receptors in rat brain, showing that the two sites are differentially distributed. High levels of both sites appear in the caudate, thalamus and superior colliculus, suggesting that adenosinergic neurons might be present in these brain regions.